SFRP4

secreted frizzled related protein 4, the group of Secreted frizzled-related proteins

Basic information

Region (hg38): 7:37905932-38025695

Links

ENSG00000106483NCBI:6424OMIM:606570HGNC:10778Uniprot:Q6FHJ7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Pyle disease (Supportive), mode of inheritance: AR
  • Pyle disease (Moderate), mode of inheritance: AR
  • Pyle disease (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pyle diseaseARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal27355534

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SFRP4 gene.

  • not provided (4 variants)
  • Pyle metaphyseal dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SFRP4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
29
clinvar
5
clinvar
34
missense
2
clinvar
51
clinvar
2
clinvar
2
clinvar
57
nonsense
3
clinvar
3
start loss
1
clinvar
1
frameshift
2
clinvar
1
clinvar
3
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
3
4
1
8
non coding
12
clinvar
12
Total 5 3 53 43 7

Highest pathogenic variant AF is 0.0000131

Variants in SFRP4

This is a list of pathogenic ClinVar variants found in the SFRP4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
7-37907482-C-G Benign (Jan 15, 2024)788420
7-37907486-CTT-C Uncertain significance (May 29, 2021)1357099
7-37907496-T-A Inborn genetic diseases Uncertain significance (Jul 27, 2021)2365999
7-37907501-C-T Pyle metaphyseal dysplasia • SFRP4-related disorder Benign (Jan 31, 2024)1332946
7-37907519-G-A Inborn genetic diseases Uncertain significance (Apr 07, 2023)2535418
7-37907562-G-T Pyle metaphyseal dysplasia • SFRP4-related disorder Benign (Jan 31, 2024)1287094
7-37907573-G-T Inborn genetic diseases Uncertain significance (Aug 15, 2022)1377522
7-37907582-G-A Inborn genetic diseases Uncertain significance (Aug 16, 2022)2307202
7-37907591-C-T Uncertain significance (May 12, 2022)2060097
7-37907604-C-T Inborn genetic diseases Uncertain significance (Jun 17, 2022)2204343
7-37907605-G-A SFRP4-related disorder Benign (May 09, 2023)1600043
7-37907606-G-A Uncertain significance (Aug 04, 2023)2420412
7-37907609-G-C Inborn genetic diseases Uncertain significance (Sep 16, 2021)2249684
7-37907636-C-T Inborn genetic diseases Likely benign (Sep 29, 2023)3160908
7-37907653-C-T Likely benign (Feb 25, 2023)2183094
7-37909611-A-ACTTACTATGGATCTTTTACTAAGCTGATCTCTCCATTTTTCAAC Uncertain significance (Sep 07, 2022)2186808
7-37909618-A-G Uncertain significance (Aug 06, 2022)2079211
7-37909624-C-T Inborn genetic diseases Uncertain significance (Mar 25, 2024)3317860
7-37909638-A-C Uncertain significance (Apr 13, 2021)1414945
7-37909673-G-A Uncertain significance (Jul 19, 2022)1416799
7-37909680-C-T Uncertain significance (Sep 26, 2022)1525259
7-37909681-C-T Likely pathogenic (Jul 28, 2023)2860973
7-37909683-GA-G Benign (Apr 16, 2022)1911002
7-37909692-T-A Likely benign (Jan 15, 2024)1955851
7-37909698-T-C Likely benign (Oct 03, 2022)1915332

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SFRP4protein_codingprotein_codingENST00000436072 6119755
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.00009260.9421257130351257480.000139
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.04592102120.9910.00001142285
Missense in Polyphen8185.5460.94686965
Synonymous0.1887577.10.9730.00000418646
Loss of Function1.72916.60.5437.73e-7180

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001480.000148
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.0007390.000739
European (Non-Finnish)0.0001060.000105
Middle Eastern0.00005440.0000544
South Asian0.00006530.0000653
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927). {ECO:0000250|UniProtKB:Q9JLS4, ECO:0000250|UniProtKB:Q9Z1N6, ECO:0000269|PubMed:12952927}.;
Disease
DISEASE: Pyle disease (PYL) [MIM:265900]: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures. {ECO:0000269|PubMed:27355534}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Wnt signaling pathway - Homo sapiens (human);Adipogenesis;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Wnt Signaling Pathway;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

pRec
0.254

Intolerance Scores

loftool
0.642
rvis_EVS
-0.25
rvis_percentile_EVS
35.99

Haploinsufficiency Scores

pHI
0.188
hipred
Y
hipred_score
0.557
ghis
0.557

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.121

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sfrp4
Phenotype
respiratory system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
positive regulation of receptor internalization;negative regulation of cell population proliferation;response to hormone;positive regulation of gene expression;cell differentiation;negative regulation of Wnt signaling pathway;regulation of BMP signaling pathway;non-canonical Wnt signaling pathway;positive regulation of apoptotic process;negative regulation of DNA-binding transcription factor activity;positive regulation of epidermal cell differentiation;phosphate ion homeostasis;canonical Wnt signaling pathway;bone morphogenesis;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of keratinocyte apoptotic process;negative regulation of non-canonical Wnt signaling pathway;negative regulation of sodium-dependent phosphate transport
Cellular component
extracellular space;nucleus;cytoplasm;cell surface
Molecular function
protein binding;Wnt-protein binding